Frank Rattray Lillie was born on June 27, 1870, in Toronto, Ontario, Canada.
His father was a wholesale druggist and accountant.
After attending a laboratory school as a youth, Lillie enrolled at the University of Toronto.
Originally intending to study theology, Lillie came under the tutelage of Robert Ramsay Wright and Archibald Macallum, who influenced Lillie to study endocrinology and embryology.
Lillie graduated in 1891 and moved to the United States.
He accepted a summer position at the Marine Biological Laboratory (MBL) in Woods Hole, Massachusetts, then became a fellow in zoology at Clark University, where he studied under Charles Otis Whitman.

In 1892 he was lured by Whitman to the newly founded University of Chicago.
 In 1894 (at the age of 24) he received the degree of Doctor of Philosophy in Zoology summa cum laude.
Between 1894-1899 he was instructor of zoology at University of Michigan.
He married Frances Williams Crane, whom he met at MBL, June 29, 1895.
Crane was the daughter of wealthy Chicago businessman Richard T. Crane.
Between 1899–1900 he was Professor of Biology at Vassar College but in 1900 he was called back to Chicago as Assistant Professor of Zoology, where he would spend the next thirty years.
In 1906, at the age of 36, he became Professor of Embryology.
In 1910 he succeeded Whitman as Chairman of the Department of Zoology and continued in that capacity until 1931.
From 1931 to 1935 he was Dean of the Division of the Biological Sciences.

While researching at the University of Chicago, Lillie also became active in the administration of the MBL.
Lillie became assistant director of the laboratory in 1900.
In 1902, Lillie was able to convince representatives from the Rockefeller Foundation, Carnegie Corporation of New York, General Education Board, and brother-in-law Charles Richard Crane to provide the institution with financial support.
After Whitman retired in 1908 to chair the zoology department, Lillie took his place as the director of the laboratory.
He held this position until 1925, when he was appointed the president of the MBL board of trustees.
Lillie oversaw the board until his retirement in 1942.
Ernest Everett Just studied under Lillie from 1909 to 1930.
He is credited with transforming the institution from a summer retreat to a long-term research institution.

At a 1925 meeting of the National Academy of Sciences (NAS), Lillie suggested that a committee be formed to begin a national oceanography organization.
The NAS agreed if Lillie could raise funds for its establishment.
With a $3 million grant from the Rockefeller Foundation, Lillie was able to establish the Woods Hole Oceanographic Institution in 1930.
He was named its first president and served in this role until 1939.
Lillie was awarded the Alexander Agassiz Medal by the NAS in 1940 for his efforts.

The American Society of Zoologists named Lillie the organization's representative to the United States National Research Council (NRC) Division of Biology and Agriculture in 1919.
Three years later, he was named the chair of the division.
From 1935 to 1939 he was served as President of the NAS.
From 1935 to 1936, he was also Chairman of the NRC.
Lillie served on the fellowship board of the latter institution for several years after his term expired.

Lillie had four daughters and adopted three sons.
He died in Chicago on November 5, 1947.
A building on the MBL campus is named after Lillie.
On May 11, 1976, the National Park Service recognized Lillie's house in Chicago as a National Historic Landmark.
Frank Rattray Lillie was born on June 27, 1870, in Toronto, Ontario, Canada. His father was a wholesale druggist and accountant. After attending a laboratory school as a youth, Lillie enrolled at the University of Toronto. Originally intending to study theology, Lillie came under the tutelage of Robert Ramsay Wright and Archibald Macallum, who influenced Lillie to study endocrinology and embryology. Lillie graduated in 1891 and moved to the United States. He accepted a summer position at the Marine Biological Laboratory (MBL) in Woods Hole, Massachusetts, then became a fellow in zoology at Clark University, where he studied under Charles Otis Whitman.
In 1892 he was lured by Whitman to the newly founded University of Chicago.  In 1894 (at the age of 24) he received the degree of Doctor of Philosophy in Zoology summa cum laude. Between 1894-1899 he was instructor of zoology at University of Michigan. He married Frances Williams Crane, whom he met at MBL, June 29, 1895. Crane was the daughter of wealthy Chicago businessman Richard T. Crane. Between 1899–1900 he was Professor of Biology at Vassar College but in 1900 he was called back to Chicago as Assistant Professor of Zoology, where he would spend the next thirty years. In 1906, at the age of 36, he became Professor of Embryology. In 1910 he succeeded Whitman as Chairman of the Department of Zoology and continued in that capacity until 1931. From 1931 to 1935 he was Dean of the Division of the Biological Sciences.
While researching at the University of Chicago, Lillie also became active in the administration of the MBL. Lillie became assistant director of the laboratory in 1900. In 1902, Lillie was able to convince representatives from the Rockefeller Foundation, Carnegie Corporation of New York, General Education Board, and brother-in-law Charles Richard Crane to provide the institution with financial support. After Whitman retired in 1908 to chair the zoology department, Lillie took his place as the director of the laboratory. He held this position until 1925, when he was appointed the president of the MBL board of trustees. Lillie oversaw the board until his retirement in 1942. Ernest Everett Just studied under Lillie from 1909 to 1930. He is credited with transforming the institution from a summer retreat to a long-term research institution.
At a 1925 meeting of the National Academy of Sciences (NAS), Lillie suggested that a committee be formed to begin a national oceanography organization. The NAS agreed if Lillie could raise funds for its establishment. With a $3 million grant from the Rockefeller Foundation, Lillie was able to establish the Woods Hole Oceanographic Institution in 1930. He was named its first president and served in this role until 1939. Lillie was awarded the Alexander Agassiz Medal by the NAS in 1940 for his efforts.
The American Society of Zoologists named Lillie the organization's representative to the United States National Research Council (NRC) Division of Biology and Agriculture in 1919. Three years later, he was named the chair of the division. From 1935 to 1939 he was served as President of the NAS. From 1935 to 1936, he was also Chairman of the NRC. Lillie served on the fellowship board of the latter institution for several years after his term expired.
Lillie had four daughters and adopted three sons. He died in Chicago on November 5, 1947. A building on the MBL campus is named after Lillie. On May 11, 1976, the National Park Service recognized Lillie's house in Chicago as a National Historic Landmark.
Frank Rattray Lillie