His older brother was Edward Charles Pickering, director of the Harvard College Observatory for three decades.

Following George Darwin, he speculated in 1907 that the Moon was once a part of the Earth and that it broke away where now the Pacific Ocean lies.

He also proposed a version of continental drift before Alfred Wegener where America, Asia, Africa, and Europe once formed a single continent, which broke up because of the separation of the Moon.

[6] In 1908, he made a statement regarding the possibility of airplanes that had not yet been invented, saying that "a popular fantasy is to suppose that flying machines could be used to drop dynamite on the enemy in time of war".

Pluto was later discovered at Flagstaff by Clyde Tombaugh in 1930, but in any case it is now known that Pluto's mass is far too small to have appreciable gravitational effects on Uranus or Neptune, and the anomalies are accounted for when today's much more accurate values of planetary masses are used in calculating orbits.

When the planet was named, he interpreted its symbol as a monogram referring to himself and Lowell by the phrase "Pickering-Lowell".