Messi, 29, scored twice against Eibar to finish the Liga season as top scorer on 37 goals, giving him 74 Golden Shoe points with each goal worth two points in the table.
Sporting Lisbon striker Bas Dost scored a hat trick in his final match against Chaves to go clear in second with 34 Portuguese Primeira Liga goals and 68 points.
Borussia Dortmund’s Pierre-Emerick Aubameyang is third with 31 goals in the Bundesliga to take the Torjagerkanone in Germany.
Both have completed their league campaigns, with only Serie A of Europe’s major leagues to play its final round of games next Sunday.
Roma striker Edin Dzeko is the top scorer in Italy with 28 goals, meaning he would need to net nine times in their last match at home to relegation-threatened Genoa just to draw level with Messi. Napoli’s Dries Mertens is on 27 goals, with Torino’s Andrea Belotti on 25.
Messi previously won the award, which counts goals in the biggest leagues as more points, in 2010, 2012 and 2013.
Since Ronaldo won the Golden Shoe as a Manchester United player in 2007-08, every winner has come from a club in Spain — though in 2013-14 Liverpool’s Luis Suarez shared the award with Ronaldo.
Golden Shoe table
- Lionel Messi, Barcelona, 74 points
- Bas Dost, Sporting Lisbon, 68
- Pierre-Emerick Aubameyang, Borussia Dortmund, 62
- Robert Lewandowski, Bayern Munich, 60
- Harry Kane, Tottenham Hotspur, 58
- Luis Suarez, Barcelona, 58
- Edin Dzeko, AS Roma, 56
- Dries Mertens, Napoli, 54
- Edinson Cavani, Paris Saint-Germain, 52.5
- Andrea Belotti, Torino, 50
- Romelu Lukaku, Everton, 50
- Anthony Modeste, Cologne, 50
- Cristiano Ronaldo, Real Madrid, 50