Reliable damage tolerant design of airframe structures relies on the accurate life prediction of fatigue cracks propagating from a detectable size to the critical size, which is challenging due to the complex load sequence effect under spectrum loading. This paper aims at gaining a further understanding of the complex influence of the loading history on fatigue damage through a detailed numerical simulation of the near-tip crack behaviour using the crack closure concept. The spectrum loading is broken down into a number of simple yet representative loading scenarios with overload/underload superimposed onto the baseline constant amplitude fatigue loading. Detailed finite element (FE) simulation of the plasticity-induced crack closure (PICC) has been carried out to catch the transient behaviour of PICC and link it to the fatigue damage. The load interaction effect has been analysed with the aim to identify the possible dominant loading cycle which could simplify the fatigue life prediction process in the industry. It is concluded that more reliable damage tolerant design can be achieved if the load sequence effect on fatigue damage can be taken into account more accurately for a structure under spectrum loadings.