Internacional beat Uruguay's Cerro 2-0 to relieve the pressure on coach Jorge Fossati and Sao Paulo drew 0-0 away to Mexican champions Monterrey.
Cruzeiro, last year's runners-up, went top of Group Seven with 10 points from five matches, the same as Velez but with the better goal difference. Colo Colo are third with four points from four games.
Man-of-the-match Thiago Ribeiro put twice South American champions Cruzeiro ahead just past the half hour when he cut inside from the left wing, beat three defenders on a mazy run and swivelled to shoot home from the edge of the box.
Thiago then laid on two goals in six minutes at the start of the second half for striker Kleber, who took his tournament-leading tally to six and squashed any hopes Velez had of fighting their way back into the match.
Kleber netted Thiago's first-time cross from the right in the 48th minute then latched on to the winger's pass down the middle and steered the ball past goalkeeper German Montoya.
Velez midfielder Leandro Somoza was sent off in the 82nd minute for a second booking.
Argentina's Estudiantes, who won the title by beating Cruzeiro in last year's final second leg at the same Mineirao ground, kept on track for the knockout phase with a 2-0 away win over Juan Aurich of Peru on Tuesday.
FOSSATI REPRIEVE
Internacional, title winners in 2006, bucked a string of poor results that had Uruguayan coach Fossati under fire with a win in Porto Alegre that put them top of Group Five, one point ahead of Cerro after four matches.
The Uruguayans, having held Inter 0-0 at home two weeks ago, were unlucky when they fell behind in the 58th minute to an own goal by defender Walter Ibanez.
Goalkeeper Damian Frascarelli had a shot from the left by Inter forward Walter covered but Ibanez stepped ahead of him to clear and sliced the ball into the net.
Striker Alecsandro rammed home the second from the rebound after Frascarelli could only parry man-of-the-match Giuliano's spectacular scissors kick from the edge of the box 13 minutes later.
Fossati had said he would resign if Inter, who had gone six matches without a win in the Gaucho state championship and Libertadores, did not beat Cerro.
Three times champions Sao Paulo are top of Group Two, two points ahead of Colombia's Once Caldas, who can take the lead if they beat eliminated and point-less Nacional of Paraguay at home on Thursday.
Monterrey are third two points further back.
