The pathogenic role of IL‐17 and GM‐CSF has been unravelled in experimental autoimmune encephalomyelitis (EAE), a murine model of multiple sclerosis (MS). However, in most models, EAE is characterised by a monophasic attack which is not representative of the relapsing nature nor the chronicity displayed in MS. Here, we used proteolipid protein peptide (PLP139‐151) to trigger EAE‐relapses (EAE‐II) in SJL mice that had recovered from a primary‐EAE episode (EAE‐I). This procedure resulted in severe and irreversible disease that, unlike EAE‐I, was not abolished by anti‐IL‐17‐mAb. In contrast, prophylactic anti‐GM‐CSF‐mAb treatment prevented EAE‐I and ‐II. Strikingly, the expression of T‐cell transcription factors and cytokines/chemokines in mice treated with anti‐GM‐CSF during both EAE episodes was silenced. Anti‐GM‐CSF‐mAb treatment administered only during EAE‐II did not completely prevent relapses but mice ultimately reached full recovery. Anti‐GM‐CSF treatment also strongly impaired and ultimately resolved monophasic MOG35‐55‐induced EAE in C57Bl/6 mice. In such protected mice, anti‐GM‐CSF treatment also prevented a further relapse induced by MOG‐revaccination. These results underscore the critical role of GM‐CSF on pro‐inflammatory mediator production. Furthermore, we observed a strong preventive and curative effect of anti‐GM‐CSF neutralisation in two EAE models, relapsing and chronic. Altogether these findings are relevant for further MS research. We investigated a chronic model of experimental autoimmune encephalomyelitis (relapse‐EAE), more representative of multiple sclerosis than primary‐EAE, to study the pathogenic role of IL‐17 and GM‐CSF. Prophylactic treatment with anti‐GM‐CSF but not anti‐IL‐17 prevented both primary‐ and relapse‐EAE. These results highlight the predominant role of GM‐CSF in chronic neuro‐inflammation.