David Mooney spurned the opportunity to cancel out Carl Baker's 10th-minute opener as his penalty was saved by goalkeeper Joe Murphy, before the Sky Blues punished the error with further goals by Franck Moussa and Leon Clarke respectively.
Coventry, who began the season with a 10-point deduction, move up to 14th in the standings, while the O's remain at the summit on goal difference after Peterborough United were left having to accept a point in a 0-0 draw with Sheffield United at London Road.
Darren Ferguson's men could have knocked Orient off top spot for the first time this season, as Posh were left frustrated by a resolute performance from the Blades to deny them victory.
James Henry registered his first goal for the club as he fired Wolves into a 1-0 lead shortly after half time, before marksman Leigh Griffiths doubled the advantage to keep Kenny Jackett's men - who have a game in hand - within touching distance of Orient and Peterborough.
Marlon Harewood struck in the dying embers, but it would prove little more than a consolation as the Robins remain rooted to the foot of the standings.
Stevenage raced into a 3-0 lead inside 20 minutes in their clash with the Railwaymen, courtesy of a Felipe Morais double either side of a Luke Freeman strike, while goals from Louis Dodds, Doug Loft and Ben Williamson secured a comfortable victory for Vale.
Results in full: Bristol City 1-2 Brentford, Coventry City 3-1 Leyton Orient, Crawley Town 0-3 Port Vale, Crewe Alexandra 0-3 Stevenage, Gillingham 2-1 Notts County, MK Dons 0-1 Carlisle United, Peterborough United 0-0 Sheffield United, Preston North End 2-2 Bradford City, Rotherham United 1-1 Tranmere Rovers, Shrewsbury Town 1-1 Colchester United, Swindon Town 1-3 Walsall, Wolverhampton Wanderers 2-0 Oldham Athletic