Diego Fabbrini and Kike were influential as Middlesbrough beat Bolton Wanderers in the Championship, while Carlisle United and Cambridge United played out an eight-goal thriller in League Two.
Aitor Karanka's Middlesbrough, losing play-off finalists last season, picked up their first league win of the campaign at the Riverside Stadium in a 3-0 triumph that saw David Nugent make his debut.
All of their goals came in the first half, with Fabbrini opening the scoring with a fierce 25-yard effort before twice setting up Kike.
Brighton and Hove Albion made it two wins from two as Tomer Hemed's 90th-minute penalty secured a 2-1 success at Fulham.
Relegated QPR remain winless after surrendering a two-goal lead to draw 2-2 against Cardiff City at Loftus Road, while Ipswich Town came from behind to see off Sheffield Wednesday 2-1, and Nottingham Forest matched that feat against Rotherham United.
Bristol City were left to rue a Luke Freeman red card as they let a 2-1 lead slip in a 4-2 defeat at home to Brentford, while Preston North End won 1-0 at fellow league newcomers Milton Keynes Dons despite playing the last seven minutes with 10 men.
The matches between Huddersfield Town and Blackburn Rovers, and Derby County and Charlton Athletic both finished 1-1. Burnley twice fought back to draw 2-2 at home to Birmingham City.
In League Two, the game of the day took place at Brunton Park as Carlisle and Cambridge played out a 4-4 draw.
Carlisle fought back from a losing position three times with Jabo Ibehre grabbing a hat-trick, as Barry Corr netted twice for the visitors.
Matt Tubbs and Gareth Roberts both scored penalties as Portsmouth beat Plymouth Argyle 2-1, and Northampton Town were 3-0 winners at home to Exeter City.
Hartlepool United, Leyton Orient and Wycombe Wanderers beat York City, Dagenham and Redbridge, and Barnet respectively to keep up their 100 per cent winning starts.
In League One, Coventry City impressed again as Newcastle United loanee Adam Armstrong scored twice in a 4-0 rout of Millwall.
Rochdale sit just behind Tony Mowbray's men after winning 2-0 at Blackpool, while Sheffield United rebounded from their opening day 4-0 loss at Gillingham to beat Chesterfield 2-0.
Swindon Town fought back to draw 2-2 at Bury, Peterborough United saw off Colchester United 2-1, and Barnsley got up and running with a 1-0 victory over league newly promoted Burton Albion.
