In a statement, the commission said the companies' activities were "largely complementary" with Ono's main activity related to fixed line telecommunication services "whereas Vodafone is mainly active in mobile telecoms".
The London-listed Vodafone, flush with cash from the sale of its Verizon Wireless stake to partner Verizon for $130 billion, agreed in March to purchase Ono for 7.2 billion euros ($10 billion).
The acquisition marks Vodafone's desire to grow in Europe following last year's 7.7-billion-euro takeover of Kabel Deutschland, the largest cable operator in Germany, and amid fast-moving consolidation within the industry.
Ono, which has about 1.9 million customers, has struggled to compete in Spain with Telefonica, Jazztel and other firms that bundle in-home services.
Vodafone meanwhile has about 14 million customers in Spain, but faces fierce competition.
Vodafone had last year sold its 45-percent Verizon Wireless holding to Verizon for $130 billion, clinching one of the biggest transactions in global corporate history.
The British group, which is the world's second-largest mobile operator by subscribers after China Mobile, has vowed to invest £19 billion over the next two years on networks and services by March 2016.
The Ono transaction meanwhile marks the latest consolidation in the fast-moving global cable industry.
US giant Liberty Global took over its British rival Virgin Media last year in a deal worth $23.3 billion.
The European Commission on Wednesday also approved the creation of Germany's biggest mobile company when it cleared the acquisition of E-plus in Germany, a unit of Dutch KPN, by Telefonica of Spain.
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