Yale patented his cylinder pin-tumbler lock in 1861. This very secure lock is still widely in use today in car doors and the outside doors of buildings. The cylinder pin-tumbler lock consists of (usually 5) pairs of bottom pins and top drivers, held in position by springs. When the right key is put into the lock, the bottom pins are pushed to the right position, allowing the key to turn and the lock to unlock. Yale introduced a combination lock a year later.

Yale opened his first lock shop in the 1840's in Shelburne, Massachusetts, specializing in bank locks. In 1868, Yale and Henry Robinson Towne founded the Yale Lock Manufacturing Company in Stamford, Connecticut, to produce cylinder locks. He dies later that year.