The Briton's Mercedes team-mate Valtteri Bottas took second spot, but was a whole 20 seconds behind the current world champion driver, who seems to be getting his mojo back after an inconsistent start to the season.
Let's be honest, after the excitement of the opening three corners, the Spanish Grand Prix was a bit of a snoozefest.
"This is more like it", Hamilton said on the team radio. We weren't happy with the performance of the cars and we needed to sort things out.
He admitted that he feared the team's rivals might have the upper hand in two weeks' time in Monaco, where Mercedes has traditionally struggled. 'The bottom line is that we were not quick enough, ' a rather glum Vettel conceded.
"Obviously we don't want to lose him and I don't think he wants to go anywhere else".
Now, to talk about the Spanish GP weekend itself, Mercedes looked to be on great form. The supersoft tyre wasn't delivering the grip and peak performance they expected and, in fact, the Ferrari drivers ended up qualifying on the soft tyre even in Q3.
"As much as I am overwhelmed by the victory here, my mind is already on Monaco, and I remember it wasn't a pleasant Sunday night past year". Yet Hamilton's win came with a degree of caution.
It was the first one-two of the season for Mercedes, which had struggled to keep pace with the Ferraris.
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On the up side, the Mercedes was particularly strong in pre-season testing in Barcelona and, as we've seen so far, the Ferrari has been right up there in Bahrain, Shanghai and Baku, so maybe this level of dominance is a one-off.
"We were assessing our options against Vettel once we saw that we didn't have the pace to pass but when he stopped on the VSC, the best strategy was to run the to end and Valtteri did an fantastic job of managing the tyres over 47 laps, the longest stint anyone made during the race".
Vettel won the Monaco race previous year, when Ferrari was 1-2 in qualifying and in the GP.
"My job is not to worry so much but preparing by extracting as much as I can from my engineers; to make sure the debrief is good, to reconnect with them later in the week once they have downloaded everything, and see that we have followed through with all the things that I have asked them to do".
After a relatively sluggish start to 2018, Mercedes AMG Petronas Motorsport's chief race engineer Andrew Shovlin has said that the team's first 1-2 finish of the season is a "great reward".
Then again, Red Bull can also never be discounted around the twisting streets of the Principality. The drivers scrambled all over the turn hoping not to hit Grosjean but Nico Hulkenburg and Pierre Gasley were collected in the mess.
The F1 bandwagon will roll into Monte Carlo for the Monaco Grand Prix on 27 May.