Worth was commissioned as a first lieutenant in March 1813, serving as an aide to (then brigadier general) Winfield Scott during the war, and developing a friendship with him.
He later named his son Winfield Scott Worth.
He distinguished himself at the battles of Chippewa and Lundy's Lane during the Niagara campaign.
In the latter battle, he was seriously wounded by grapeshot in the thigh.
He was not expected to survive, but after a year's confinement, he emerged with the breveted rank of Major—though he would remain lame for the rest of his life.
Also as a brevet Major Worth uttered his most famous words that are now inscribed in West Point's "Bugle Notes", a book of knowledge all cadets must know by heart.
They are as follows:
 But an officer on duty knows no one—to be partial is to dishonor both himself and the object of his ill-advised favor.
What will be thought of him who exacts of his friends that which disgraces him?
Look at him who winks at and overlooks offences in one, which he causes to be punished in another, and contrast him with the inflexible soldier who does his duty faithfully, notwithstanding it occasionally wars with his private feelings.
The conduct of one will be venerated and emulated, the other detested as a satire upon soldiership and honor.

 
— Brevet Major William Jenkins Worth
After the war he was Commandant of Cadets at West Point and would rise to the rank of Colonel in 1838 when he was put in command of the newly created Eighth Infantry Regiment.
 Using his own tactics he successfully prosecuted the Second Seminole War in Florida and was made a brevet brigadier general in 1842.
 Eventually, he convinced Secretary of War John C. Spencer to allow the remaining Indians in the territory to confine themselves to an unofficial reservation in southwest Florida, and declared an official end to the war in August of that year.
Worth was commissioned as a first lieutenant in March 1813, serving as an aide to (then brigadier general) Winfield Scott during the war, and developing a friendship with him. He later named his son Winfield Scott Worth. He distinguished himself at the battles of Chippewa and Lundy's Lane during the Niagara campaign. In the latter battle, he was seriously wounded by grapeshot in the thigh. He was not expected to survive, but after a year's confinement, he emerged with the breveted rank of Major—though he would remain lame for the rest of his life. Also as a brevet Major Worth uttered his most famous words that are now inscribed in West Point's "Bugle Notes", a book of knowledge all cadets must know by heart. They are as follows:
 But an officer on duty knows no one—to be partial is to dishonor both himself and the object of his ill-advised favor. What will be thought of him who exacts of his friends that which disgraces him? Look at him who winks at and overlooks offences in one, which he causes to be punished in another, and contrast him with the inflexible soldier who does his duty faithfully, notwithstanding it occasionally wars with his private feelings. The conduct of one will be venerated and emulated, the other detested as a satire upon soldiership and honor.
 
— Brevet Major William Jenkins Worth
After the war he was Commandant of Cadets at West Point and would rise to the rank of Colonel in 1838 when he was put in command of the newly created Eighth Infantry Regiment.  Using his own tactics he successfully prosecuted the Second Seminole War in Florida and was made a brevet brigadier general in 1842.  Eventually, he convinced Secretary of War John C. Spencer to allow the remaining Indians in the territory to confine themselves to an unofficial reservation in southwest Florida, and declared an official end to the war in August of that year.
William J. Worth