Brett McLean and Milan Hejduk also scored while Tyler Arnason and Ian Laperriere had two assists apiece for the Avalanche (2-2-2), who have stops in Ottawa on Thursday and Montreal on Saturday, Jose Theodore's first game at the Bell Centre back since being dealt by the Habs to the Avs last March.
Bates Battaglia had the lone goal for the Maple Leafs (3-2-2), who played their worst game of the season. The Leafs were flat for most of the night and devoid of the kind of energy displayed in most games this season.
Theodore, meanwhile, watched from the bench as backup Peter Budaj stopped 27 shots for the win, the Slovak looking sharp in earning his first win of the season in only his second start.
Andrew Raycroft was also solid for the Leafs, stopping 22 shots in defeat. He robbed star centre Joe Sakic with a pad save in the first period and stoned Arnason in the second.
The loss will dampen the spirit of local fans buoyed by Toronto's surprisingly strong start under new head coach Paul Maurice. Back-to-back games at Columbus on Friday and at home to the New York Rangers on Saturday will be a nice early-season test to see how Maurice's Leafs bounce back following a clunker.
It all started so well Wednesday for the Leafs before a quiet crowd of 19,463 at Air Canada Centre. Toronto's fourth line, which played one shift Saturday, opened the scoring 2:22 into the first period, Battaglia finding the top corner over Budaj's glove side after some good forechecking by linemates Wade Belak and John Pohl.
McLean tied it 1-1 midway through the first period, shovelling in a rebound over a sprawled Raycroft.
Leafs winger Jeff O'Neill thought he had the go-ahead goal five minutes into the second period but referee Mike Hasenfratz blew his whistle before the puck crossed the line. Mats Sundin's effort was also waived off midway through the third period during a 5-on-3 power play when he clearly re-directed the puck with a high stick.
Liles gave Colorado its first lead of the game with 4:02 left in the middle period, somehow sliding a shot in while falling. He then added the insurance goal 6:22 into the third period, sneaking a nice wrist shot past Raycroft's stick side.
Hejduk also beat Raycroft stick side with a wrist shot on a 2-on-1 break with 2:56 remaining, a goal that emptied the Air Canada Centre in a hurry.
Notes: Sundin was honoured before the game for reaching the 500-goal plateau ... Colorado defenceman Karlis Skrastins appeared in his 439th consecutive game, the longest active streak in the NHL and the second longest by a defenceman in NHL history. Former Leaf Tim Horton owns the record for defencemen at 486 ... Defencemen Pavel Kubina (knee), Andrew Wozniewski (shoulder), Carlo Colaiacovo (head), Staffan Kronwall (ankle) and forwards Ben Ondrus (contusion) and Nik Antropov (leg) were out for Toronto while forward Alexander Suglobov was a healthy scratch. Ondrus and Antropov are close to returning ... Forwards Pierre Turgeon (shoulder), George Parros (shoulder) and Brad May (shoulder) and defencemen Jordan Leopold (hernia) and Cody McCormick (chest) were out for Colorado.