He joined the Christian Democratic Nationalist Party (PN) in the early 1960s, establishing a reputation as a reserved but determined and capable constituency official. He entered parliament in 1969. In 1977, having served in a number of senior party posts, including president of the Administrative and General Councils, he was elected party leader, succeeding Dr. Gorg Borg-Oliver. Under his direction, younger and more open-minded and socially conscious elements were brought into the PN.  

Dr Fenech-Adami's style of leadership immediately generated great support amongst the electorate, and in the 1981 elections the PN obtained an absolute majority of the vote. The long and difficult years of opposition, however, continued for another five years until constitutional changes were made to guarantee that the party winning an absolute majority of votes would have a parliamentary majority. In the 1987 elections, the PN again won an absolute majority and, this time, took over government with Dr Eddie Fenech-Adami as Prime Minister. Dr Fenech-Adami led the PN to another electoral victory in 1992, with an increased majority for his government.  

Between 1987 and 1996, Prime Minister Fenech-Adami ushered in a major period of change for Malta . The country's physical infrastructure was completely overhauled as were the legal and business structures. Sixteen years of socialist policies were rolled back and trade was liberalised whilst telecommunications, banking and financial services were deregulated and/or privatised. The result was nine years of economic growth, averaging 5% per annum in real terms. Malta also began a period of integration with the European Union when its application was presented in 1990.  

The PN lost the 1996 election, in part because of disgruntlement following the introduction of Value Added Tax. The period in opposition, during which the elected Government suspended Malta ’s application to the European Union, was, however, short-lived as the Labour Government was unable to retain its majority in Parliament.  In September 1998, Dr Fenech-Adami led the PN to another electoral victory, this time winning its largest majority since the second world war.  He immediately reactivated Malta ’s EU application and succeeded in fully concluding negotiations by December 2002.  In April 2003 Dr Edward Fenech-Adami was again confirmed as Prime Minister, following yet another electoral victory.  

On the 16^th April, 2003, Prime Minister Fenech - Adami signed Malta’s Accession Treaty with the European Union, together with nine other Heads of Government of countries set to become EU members in May 2004.  On the 7^th February 2004 , Dr Fenech-Adami decided to tender his resignation as Nationalist Party Leader, upon reaching his 70^th Birthday and was succeeded by Dr Lawrence Gonzi.  On the 23^rd March 2004 , Dr Edward Fenech - Adami resigned his premiership as well as his parliamentary seat.