Millwood left the game with what club officials said was a strained groin muscle he suffered while warming up for the seventh inning.
He had walked one with six strikeouts, and had faced the minimum numbers of batters, but was unable to continue and was followed to the mound by Charlie Furbush, Stephen Pryor, Lucas Luetge, Brandon League and Tom Wilhelmsen.
League worked out of an eighth-inning jam to save the game, as well as the no-hitter, and Wilhelmsen then retired the side in order in the ninth to complete the rare multiple masterpiece.
The last combined no-hitter in the majors came June 11, 2003, when six members of the Houston Astros shut down the New York Yankees 8-0. Roy Oswalt started that game, but left with an injury in the second inning.
The six pitchers in that contest had been the most ever involved in a no-hitter. The Mariners tied the record Friday.
Millwood left with the game scoreless and the win went to Pryor (1-0), who, remarkably, was part of a no-hit performance in his first major league victory. He was recalled from Class AAA Tacoma last week and this was only the fourth appearance of his big league career.
Pryor came on with two out in the seventh to replace Furbush and struck out Juan Rivera to end the inning. Pryor then walked the first two batters in the eighth and League eventually worked out of trouble in that inning.
Wilhelmsen's perfect ninth gave him his third save.
This was the fourth no-hitter of the major-league season, the others being thrown by Philip Humber of the Chicago White Sox in a perfect game, Jered Weaver of the Los Angeles Angels and Johan Santana of the New York Mets.
The all-time record for most no-hitters in one year is eight, established in 1884. More recently there were seven no-hitters thrown in both 1990 and 1991.
It was Seattle's third no-hitter, Chris Bosio having thrown one in 1993 and Randy Johnson the other in 1990.