After Wehrle's discharge he enrolled in a Master of Fine Arts graduate program at Pratt Institute in Brooklyn, New York.
There, in collaboration with fellow students, he helped devise a multimedia theatrical experience involving film, dance, and projections in a theater designed by James Petrillo.

After graduation in 1969, Wehrle moved to San Francisco, where he taught at the De Young Museum and California College of Arts and Crafts.
In 1973, he quit his teaching position to follow an opportunity to build a wilderness log cabin in Montana.
After a winter in Whiskey Gulch, he returned to the Bay Area, where he worked as a baker and carpenter for a brief time.
 He was hired under the comprehensive Employees Training Act in 1974 to work, once again, at the De Young Museum.
Here Wehrle devised and painted his first exterior mural EB-1942, a 16x 48 oil painting on panels drawn from his Montana experiences.

During this project, he met painter John Rampley and together they designed and painted the second mural Positively Fourth Street in the De Young staff parking lot in 1976.
Wehrle describes the inspiration for this painting as the result of being stuck in rush hour traffic on the 101 freeway approach to the Bay Bridge.

Following this period of relative stability Wehrle resumed his nomadic existence, moving between Montana and Los Angeles.
In 1978 he received a California Arts Council grant to paint Fall of Icarus on a 20x90 foot wall in Venice Beach'.
During this period, he met other members of the Los Angeles mural movement, Terry Schoonhoven, Vic Henderson, Art Mortimer, Kent Twitchell and Judy Baca.
After painting a private commission for movie producer Carl Borack on his residence in Beverly Hills, Wehrle moved back to Bay Area.
There he painted Ancisco, on the wall of a Berkeley bakery, the first of many projects still extant in California.

In 1980, scientists Tom White and Kary Mullis commissioned Wehrle to paint a mural for their biotech lab at newly formed Cetus Corporation.
After completing and installing Return of Jonah, Cetus CEO, Ron Cape commissioned Wehrle to paint …paging Dr. Crick in situ at their Berkeley Headquarters.
Subsequently, these paintings were transferred, along with the furniture, to Chiron Corporation; later Novartis bought the company.
The paintings have now been moved to the Novartis corporate collection in Switzerland, no longer viewable by the general public.
Kary Mullis later won the Nobel Prize for his discovery of Polymerase chain reaction.
An image of Return of Jonah serves as the home page header of the PCR website and is also used as the cover of Paul Rabinow's entertaining story of Cetus's scientific milieu, Making PCR.

In 1983, Wehrle was chosen as one of 10 official muralists for the 1984 Summer Olympic Games in Los Angeles.
These were the first artworks that Caltrans allowed directly on the freeway.
Richard Wyatt, Alonzo Davis, Judy Baca, Kent Twitchell  Glenna Boltuch, Roderick Sykes, Terry Schoonhoven, Willie Heron, Frank Romero, and John Wehrle were each commissioned to decorate retaining walls on the 110 and 101 freeways connecting the Olympic venues.
The works survived until the mid-1990s, when graffiti tagging took its toll on the public works.
In 2004 the state of California funded restoration of some of the murals including Wehrle's 207-foot mural Galileo, Jupiter, Apollo.
Subsequent vandalism caused Caltrans to paint over the artworks, substituting smaller digital prints on their previous locations.
After a 2013 vote by the Los Angeles City Council on lifting a ban against mural painting, the Mural Conservancy of Los Angeles (MCLA), in cooperation with Caltrans, began to restore the work.

During the 1980s, Wehrle exhibited work with Koplin Gallery.
This led to a commission Knockout for Kate Mantilini Restaurant, a modern-day roadhouse on Wilshire and Doheney in Los Angeles, designed by Morphosis architects for owner Marilyn Lewis.
The building was given a Progressive Architecture Award and architect Thom Mayne later won the Pritzker Prize.
Wehrle also completed War and Pea
After Wehrle's discharge he enrolled in a Master of Fine Arts graduate program at Pratt Institute in Brooklyn, New York. There, in collaboration with fellow students, he helped devise a multimedia theatrical experience involving film, dance, and projections in a theater designed by James Petrillo.
After graduation in 1969, Wehrle moved to San Francisco, where he taught at the De Young Museum and California College of Arts and Crafts. In 1973, he quit his teaching position to follow an opportunity to build a wilderness log cabin in Montana. After a winter in Whiskey Gulch, he returned to the Bay Area, where he worked as a baker and carpenter for a brief time.  He was hired under the comprehensive Employees Training Act in 1974 to work, once again, at the De Young Museum. Here Wehrle devised and painted his first exterior mural EB-1942, a 16x 48 oil painting on panels drawn from his Montana experiences.
During this project, he met painter John Rampley and together they designed and painted the second mural Positively Fourth Street in the De Young staff parking lot in 1976. Wehrle describes the inspiration for this painting as the result of being stuck in rush hour traffic on the 101 freeway approach to the Bay Bridge.
Following this period of relative stability Wehrle resumed his nomadic existence, moving between Montana and Los Angeles. In 1978 he received a California Arts Council grant to paint Fall of Icarus on a 20x90 foot wall in Venice Beach'. During this period, he met other members of the Los Angeles mural movement, Terry Schoonhoven, Vic Henderson, Art Mortimer, Kent Twitchell and Judy Baca. After painting a private commission for movie producer Carl Borack on his residence in Beverly Hills, Wehrle moved back to Bay Area. There he painted Ancisco, on the wall of a Berkeley bakery, the first of many projects still extant in California.
In 1980, scientists Tom White and Kary Mullis commissioned Wehrle to paint a mural for their biotech lab at newly formed Cetus Corporation. After completing and installing Return of Jonah, Cetus CEO, Ron Cape commissioned Wehrle to paint …paging Dr. Crick in situ at their Berkeley Headquarters. Subsequently, these paintings were transferred, along with the furniture, to Chiron Corporation; later Novartis bought the company. The paintings have now been moved to the Novartis corporate collection in Switzerland, no longer viewable by the general public. Kary Mullis later won the Nobel Prize for his discovery of Polymerase chain reaction. An image of Return of Jonah serves as the home page header of the PCR website and is also used as the cover of Paul Rabinow's entertaining story of Cetus's scientific milieu, Making PCR.
In 1983, Wehrle was chosen as one of 10 official muralists for the 1984 Summer Olympic Games in Los Angeles. These were the first artworks that Caltrans allowed directly on the freeway. Richard Wyatt, Alonzo Davis, Judy Baca, Kent Twitchell  Glenna Boltuch, Roderick Sykes, Terry Schoonhoven, Willie Heron, Frank Romero, and John Wehrle were each commissioned to decorate retaining walls on the 110 and 101 freeways connecting the Olympic venues. The works survived until the mid-1990s, when graffiti tagging took its toll on the public works. In 2004 the state of California funded restoration of some of the murals including Wehrle's 207-foot mural Galileo, Jupiter, Apollo. Subsequent vandalism caused Caltrans to paint over the artworks, substituting smaller digital prints on their previous locations. After a 2013 vote by the Los Angeles City Council on lifting a ban against mural painting, the Mural Conservancy of Los Angeles (MCLA), in cooperation with Caltrans, began to restore the work.
During the 1980s, Wehrle exhibited work with Koplin Gallery. This led to a commission Knockout for Kate Mantilini Restaurant, a modern-day roadhouse on Wilshire and Doheney in Los Angeles, designed by Morphosis architects for owner Marilyn Lewis. The building was given a Progressive Architecture Award and architect Thom Mayne later won the Pritzker Prize. Wehrle also completed War and Pea
John O. Wehrle