Carlos Vinicius struck the winner for Fulham to leave Luton Town at the foot of the table and still seeking their first point of the season.
The substitute was making his first appearance of the campaign and scored less than five minutes after coming on in the second half.
Luton had frustrated the visitors in the first half, with Jacob Brown hitting the post with a header.
Fulham’s second Premier League win lifts them into ninth place.
The Hatters had managed to carve out better chances than the hosts prior to the winner despite their rigidly defensive set-up, with Amari’i Bell missing a chance from close range when unmarked in the area early in the second half.
But the introduction of Vinicius, making his first appearance of the season, and new signing Alex Iwobi, gave the hosts the creativity that was required to break down the spirited Premier League newcomers.
Silva’s substitutions make the difference
Fulham’s last outing came amid a turbulent few days for the Cottagers, with Joao Palhinha’s proposed move to Bayern Munich collapsing at the end of the transfer window, before a painful 5-1 defeat by Manchester City.
That loss at Etihad Stadium had seen Fulham manager Marco Silva infuriated by the VAR decision that allowed Nathan Ake’s goal to stand, but the Portuguese cut a calmer figure on his 100th game in charge at Craven Cottage.
His recall of Palhinha, Fulham’s player of the season during the last campaign, gave his side an early edge but they faded and looked short of ideas to combat Luton’s resilience as the first half wore on.
But the double substitution, with Harrison Reed and Raul Jimenez making way for Iwobi and Vinicius, proved to be crucial and gave them a cutting edge and creativity. Iwobi was involved in the build-up to the goal before Willian’s chipped cross from the left that Luton goalkeeper Thomas Kaminski spilled into the path of Vinicius in the six-yard box.
Despite the single-goal advantage Fulham looked comfortable for much of the rest of the game, holding out to seal the win and their first home clean sheet in the league since beating Nottingham Forest in February.
Missed chances cost Luton dearly
The Hatters will leave west London wondering what might have been, having spurned several chances to score despite spending long periods absorbing pressure from the home side.
Tahith Chong shot straight at Bernd Leno after just four minutes, and Carlton Morris fired wide of the target from a tight angle 20 minutes later.
The miss from Morris was followed by Brown’s effort on to the woodwork, the recent signing from Stoke hitting the post when left unmarked from Issa Kabore’s cross from the right.
Luton started the second half promisingly, with Bell shooting wide from Brown’s cross, and another fine chance went begging in stoppage time when Tom Lockyer’s glancing header flew wide of the target from inside the area.
Rob Edwards’ side were a menace on the break throughout, but must start capitalising on those rare chances having become just the second side to lose the first four games in their first Premier League season after Swindon Town in 1993-94.