Kerley timed his dip perfectly to clock 9.86 seconds as Marvin Bracy (28) took silver and Trayvon Bromell (27) bronze, both with 9.88 seconds, but Bracy edging it by two thousandths of a second.
A fourth American in the final, defending champion Christian Coleman (26), finished sixth.
Carl Lewis led clean sweeps in 1983 and 1991 but no nation has managed it since.
There was nothing between the medallists once they were into their running, and with Bromell out in lane eight and the other two side-by-side in three and four it was an impossible finish to call.
As each name, alongside the Stars and Stripes, appeared on the giant screen, the home crowd increased the volume of their cheers, greeting confirmation of the 1-2-3 with a chant of "USA".
That would have been more impressive had the 12,500 capacity stadium been anywhere near full on what should be the biggest night of the championships.
The empty seats will be a huge disappointment for the organisers and World Athletics.
Kerley, of course, was not in the slightest bit worried about that. "I said we were going to do it and we did it - USA, baby," he said in a trackside interview.
Olympic silver medallist Kerley was the form runner in the field. He posted the year's leading time and a personal best of 9.76 on the same Eugene track when winning the US trials last month, and his 9.79 on Friday was the fastest-ever world championships heat time.
He is one of only three men, along with South Africa's Wayde van Niekerk and fellow American Michael Norman, to have broken 10 seconds in the 100m, 20 seconds in the 200m and 44 seconds in the 400m.
And the 27-year-old is now the only man to have medalled at both 100m and 400m having finished third over one lap in 2019.
For Bromell, second-fastest in the world this year, the bronze was some sort of consolation after the Tokyo Olympics, where he failed to make the final after entering the Games as favourite.
Jamaican Oblique Seville (21), the fastest of the semi-final qualifiers, finished fourth in 9.97, while Italy's Olympic champion Lamont Jacobs (27) withdrew before the semi-finals due to injury.
In the women's 100m event, Jamaican trio Elaine Thompson-Herah (30), Shelly-Ann Fraser-Pryce (35) and Shericka Jackson (28) rolled through the heats but it was Briton Dina Asher-Smith (26) advancing with the quickest time.
Nearly a year since she produced the second-fastest 100m of all time at the springy Hayward Field, back-to-back Olympic sprint double champion Thompson-Herah won her heat in 11.15, easing up at the 60m mark.
World leader Fraser-Pryce also preserved her energy, winning her heat in 10.87 while Jackson, the other member of the trio who took all three Tokyo Olympics podium spots, came home first in her heat in 11.02.
Meanwhile, one throw was all it took for Chase Ealey (27) to make history on Saturday as she won the United States' first women's shot put title at the World Championships, denying China's Gong Lijiao (33) a third successive gold medal.
The 27-year-old let out a roar as she threw 20.49 metres with her opening attempt, a mark that proved untouchable through six rounds, though Chinese Olympic champion Gong came close with her fifth try, which fell just 10cm short.
